Diagnostic features of acquired dermal melanocytosis of the face and extremities.

Acquired dermal melanocytosis of the face and extremities (ADMFE) is an unusual form of acquired dermal melanocytosis (ADM). In this paper, we report a case of ADMFE and review the published literature. Our review highlights several clinical differences between ADMFE and ADM: (i) more frequent involvement of the nasal alae in ADMFE than in ADM, (ii) less frequent involvement of the cheeks in ADMFE than in ADM, (iii) limbs affected in all cases of ADMFE but in few cases of ADM, and (iv) frequent involvement of conjunctiva and/or gingiva in ADMFE but very rare involvement in ADM. These findings strongly support the hypothesis that ADMFE is clinically distinct from the classic form of ADM, and gaining an understanding of its phenotype will enable accurate diagnosis and early intervention by Q-switched laser therapy, which should benefit those patients with disease-related cosmetic issues.

Loss-of-function mutations in the gene encoding filaggrin underlie a Japanese family with food-dependent exercise-induced anaphylaxis.

BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) is a serious food allergy in which anaphylaxis develops when exercise is performed within several hours after food intake. The precise mechanism underlying allergic sensitization in FDEIA has been an important issue but remains poorly understood. OBJECTIVES: We aimed to elucidate the pathomechanism including the route of allergen sensitization involved in FDEIA. METHODS: A Japanese family with wheat-dependent exercise-induced anaphylaxis (WDEIA), a specific form of FDEIA, were clinically examined. Mutation analysis of the gene encoding filaggrin (FLG) was also performed. RESULTS: Two of the family members were confirmed as WDEIA on the basis of their medical history and positive provocation test results. Notably, the two affected individuals in the family had concomitant ichthyosis vulgaris. Mutation analysis of FLG revealed that they carry one or more loss-of-function mutations that have not been described in the Japanese population. CONCLUSION: These results indicate that FLG mutations might be involved in the pathogenesis of WDEIA in the present case.

Comprehensive screening for a complete set of Japanese-population-specific filaggrin gene mutations.

Mutations in FLG coding profilaggrin cause ichthyosis vulgaris and are an important predisposing factor for atopic dermatitis. Until now, most case-control studies and population-based screenings have been performed only for prevalent mutations. In this study, we established a high-throughput FLG mutation detection system by real-time PCR with a set of two double-dye probes and conducted comprehensive screening for almost all of the Japanese-population-specific FLG mutations (ten FLG mutations). The present comprehensive screening for all ten FLG mutations provided a more precise prevalence rate for FLG mutations (11.1%, n = 820), which seemed high compared with data of previous reports based on screening for limited numbers of FLG mutations. Our comprehensive screening suggested that population-specific FLG mutations may be a significant predisposing factor for hay fever (odds ratio = 2.01 [95% CI: 1.027-3.936, P < 0.05]), although the sample sizes of this study were too small for reliable subphenotype analysis on the association between FLG mutations and hay fever in the eczema patients and the noneczema individuals, and it is not clear whether the association between FLG mutations and hay fever is due to the close association between FLG mutations and hay fever patients with eczema.

Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis.

BACKGROUND: Nagashima-type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma (PPK). Very recently, putative loss-of-function mutations in SERPINB7, which encodes a member of the serine protease inhibitor superfamily and is abundantly expressed in the epidermis, have been identified as a cause of NPPK. OBJECTIVES: To confirm further the role of SERPINB7 mutations in the pathogenesis of NPPK. METHODS: We analysed 10 Japanese families with NPPK using Sanger and/or whole-exome sequencing. RESULTS: We identified one novel and three recurrent null mutations in SERPINB7. In all the families, the NPPK trait was inherited in an autosomal recessive manner; in one of the families, there was pseudodominant inheritance, which had not been described in NPPK. CONCLUSIONS: These data clearly provide further evidence that NPPK is caused by loss-of-function mutations in SERPINB7.

A novel splice site mutation in NCSTN underlies a Japanese family with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic follicular occlusive disease with characteristic recurrent draining sinuses, skin abscesses and disfiguring scars, mainly involving the axilla, groin, perianal and perineal regions. While most HS cases are nonfamilial, familial cases showing autosomal dominant inheritance have been reported. Recently, loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of familial HS in the Chinese and British populations. OBJECTIVES: To identify mutations in the genes encoding γ-secretase in Japanese patients with familial and nonfamilial HS. METHODS: Two affected and three unaffected individuals from a Japanese family with familial HS and nine patients with nonfamilial HS were recruited. We conducted mutation analysis of the γ-secretase genes in Japanese patients with familial and nonfamilial HS. RESULTS: A novel splice site mutation in the nicastrin gene NCSTN, one of the six key component genes encoding γ-secretase, was identified in the patients with familial HS. Neither unaffected individuals in the family nor 100 ethnically matched control alleles carry this mutation. None of the nine patients with nonfamilial HS carry nonsense, frameshift or splice site mutations in this gene. CONCLUSIONS: A novel splice site mutation, c.582+1delG, in NCSTN was identified in the familial patients with HS. We also reveal for the first time that a γ-secretase gene mutation is not linked to the development of nonfamilial HS. These results would further pave the way to a better understanding of the contribution of γ-secretase and other genes to the pathogenesis of HS and to the development of a new therapeutic strategy for HS.

A severe and refractory case of anti-p200 pemphigoid resulting in multiple skin ulcers and scar formation.

Anti-p200 pemphigoid is a recently described autoimmune blistering skin disease that is characterized by the presence of autoantibodies against an unidentified 200-kDa dermal autoantigen. Most of the previous cases have been successfully treated using mild-to-moderate immunosuppressive therapies, which resulted in a good prognosis. We report here a severe and refractory case of anti-p200 pemphigoid that developed in a 53-year-old woman, in which blisters led to multiple skin ulcers, followed by severe scar formation. In the present case, methylprednisolone pulse therapy was effective enough to reduce the disease activity.

In vitro biocompatibility of a new titanium-29niobium-13tantalum-4.6zirconium alloy with osteoblast-like MG63 cells.

BACKGROUND: Titanium-29niobium-13tantalum-4.6zirconium (TiNb) has recently been developed as a new implant material. TiNb is composed of non-toxic elements and has a lower modulus of elasticity than the other titanium alloys. However, its biocompatibility has not been adequately characterized. The aim of this study was to evaluate the biocompatibility of TiNb using an osteoblast-titanium co-culture system. METHODS: MG63 cells were cultured on three kinds of titanium disks: TiNb, pure titanium (pTi), and titanium-6aluminum-4vanadium (TiAl), prepared with two different surfaces, a polished and acid-etched surface and a machined-grooved surface. The surface topography and roughness were evaluated by scanning electron microscopy (SEM). After 48 hours culture, the number of proliferating cells and prostaglandin E2 (PGE2) production in the culture supernatant were determined. RESULTS: There was no significant difference in surface roughness among the three titanium disks with a polished and acid-etched surface. After 48 hours of culture, the number of cells was significantly reduced on pTi and TiAl compared to TiNb and the control. PGE2 production was significantly higher on pTi than on TiAl, TiNb, and the control. We further examined the effect of surface roughness on PGE2 production using machine-grooved titanium disks. While pTi and TiAl stimulated the production of PGE2 depending on surface roughness, roughened TiNb did not affect PGE2 production. CONCLUSIONS: These results suggest that TiNb may exhibit favorable biocompatibility because it has an efficient surface topography for cell proliferation, and the level of PGE2 production does not depend on surface roughness. We conclude that TiNb may be useful as an implant material.

Synthesis of (1-->4)-beta-D-xylo-oligosaccharides of dp 4-10 by a blockwise approach.

Dibutyltin oxide-mediated regioselective chloroacetylation of methyl 1-thio-beta-xylobioside, followed by treatment of the product with 4-methylbenzoyl chloride-pyridine, gave methyl 4-O-chloroacetyl-2,3-di-O-(4-methylbenzoyl)-beta-D-xylopyranosyl-(1-->4) -2.3-di - O-(4-methylbenzoyl)-1-thio-beta-D-xylopyranoside (18) in 70% yield. Coupling of 18 with benzyl alcohol afforded the disaccharide benzyl beta-glycoside, which was O-dechloroacetylated to provide methyl 2,3-di-O-(4-methylbenzoyl)-beta-D-xylopyranosyl-(1-->4)-2,3-di-O-(4- methylbenzoyl)-1-thio-beta-D-xylopyranoside (20). A homologous series of (1-->4)-beta-D-xylo-oligosaccharides from the tetra- to the deca-saccharide have been synthesized in a blockwise manner by using 20 as the glycosyl acceptor, 18, methyl 1-thio-beta-xylobioside pentaacetate, and methyl 1-thio-beta-xylotrioside heptaacetate as the glycosyl donors, and a combination of N-iodosuccinimide-silver triflate as the promoter.

Synthesis of 2- and 4-nitrophenyl beta-glycosides of beta-(1-->4)- D-xylo-oligosaccharides of dp 2-4.

2- and 4-Nitrophenyl beta-D-xylopyranosides (4 and 5) were transformed, via dibutyltin oxidemediated acylation, into the corresponding 2,3-di-O-benzoyl derivatives 11 and 15. Xylobiose and xylotriose were easily isolated by charcoal column chromatography from a commercially available material and converted into the di- and trisaccharide methyl 1-thio-beta-glycosides 36 and 37. The 2-and 4-nitrophenyl beta-glycosides of the beta-(1-->4)-D-xylo-oligosaccharides of dp 2-4 were synthesized by N-iodosuccinimide-silver triflate-promoted condensation using 11 and 15 as the glycosyl acceptors and ethyl 1-thio-beta-D-xylopyranoside triacetate 16, 36, and 37 as the glycosyl donors. Also described are an improved preparation of 4 and 5, and the synthesis of 1-naphthyl beta-D-xylopyranoside, as well as an alternative approach to the 2- and 4-nitrophenyl beta-xylobiosides.

Jejunal interposition hepaticoduodenostomy for congenital dilatation of the bile duct (choledochal cyst).

In eight cases of congenital dilatation of the bile duct encountered in our institution during the past 3 years, jejunal interposition hepaticoduodenostomy was performed following resection of the involved bile duct. This procedure has no serious technical difficulties but appears to have some advantages over conventional techniques. The postoperative course of the patients has been favorable for a mean period of 1 year and 5 months up to the present. A further follow-up study is necessary before definite conclusions can be drawn.

Adult T-cell leukemia occurring in mother and son.

We report two cases of adult T-cell leukemia in which the disease developed in a mother, aged 62 years, and her son, aged 41 years, less than four months apart. Both mother and son showed abnormal karyotypes and high titers of adult T-cell leukemia-associated antibody.

Incidence of adult T-cell leukemia-lymphoma and its familial clustering.

The yearly incidence of ATLL in the Uwajima district is 6.6 patients per 100,000 inhabitants aged over 40. The yearly morbidity rate from ATLL of persons in this district who are positive for HTLV-antibody and older than 40 is 1 patient per 1,631. Familial occurrence was observed in 9/38 families available for pedigree analyses. Even in the endemic area, the existence of positive HTLV antibody is remarkably high in ATLL families, suggesting that HTLV has been transmitted from generation to generation mainly within these particular families.